Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer

This study has been completed.
Taiho Pharmaceutical Co., Ltd.
Information provided by:
Japan Clinical Cancer Research Organization Identifier:
First received: March 5, 2008
Last updated: June 27, 2011
Last verified: June 2011

The purpose of this study is compare overall survival of the test arm (CPT-11/S-1 combination) to the control arm (CPT-11 alone) in the subjects with S-1 refractory advanced gastric cancer.

Condition Intervention Phase
Gastric Cancer
Drug: S-1 + irinotecan
Drug: irinotecan
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II/III Trial of Second Line Chemotherapy Comparing CPT-11 Monotherapy Versus S-1/CPT-11 Combination for S-1 Refractory Gastric Cancer

Resource links provided by NLM:

Further study details as provided by Japan Clinical Cancer Research Organization:

Primary Outcome Measures:
  • In phase II part, progressive disease rate will be measured for the safety. In phase III part, overall survival will be measured for the benefit of doublet. [ Time Frame: Phase II: 6 weeks from treatment, Phase III: 2 years OS from randomization ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse events, response rates, progression free survival, time to treatment failure, change over rates to 3rd line [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: March 2008
Study Completion Date: June 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
CPT-11+ S-1
Drug: S-1 + irinotecan
Irinotecan 150mg/m2 iv on day one and S-1 po days 1 to 14 every 3 weeks until PD
Other Names:
  • TS-1
  • CPT-11
Active Comparator: B
Drug: irinotecan
Irinotecan 150mg/m2 iv on day one every two weeks until PD
Other Name: CPT-11

Detailed Description:

Standard chemotherapy for advanced gastric cancer (AGC) in the US is Cisplatin/5-FU (CF) or docetaxel/CF (DCF), is in Europe epirubicin/CF (ECF) or epirubicin/oxaliplatin/ capecitabine (EOX). Until 2006, there was no evidence of standard chemotherapy for AGC in Japan. In 2007, by the results of JCOG9912 trial (5-FU alone vs. CPT-11/CDDP vs S-1) and SPIRITS trial (S-1 alone vs. S-1/CDDP), S-1/CDDP is regarded as a new standard regimen in Japan. In 2008, by the results of TOP-002 trial (s-1 alone vs. S-1/CPT-11), S-1/CPT-11 could not show the superiority to S-1 alone. One of the other phase III trials, JACCRO GC-03 trial (S-1 alone vs. S-1/docetaxel, NCT00287768) is now ongoing. However, the position of CPT-11 in the treatment of AGC will be regarded as a second-line.

In Japan there is a controversy for the treatment of S-1 refractory gastric cancer. The controversy is continuing S-1 (like FOLFOX to FOLFIRI) or not as a second-line. After the successful adjuvant S-1 results (ACTS-GC trial), the same problem will occur in the patients who are recurrent from adjuvant S-1.

Then, we conducted a phase II/III trial of CPT-11 with or without S-1 in the treatment of first-line S-1 refractory AGC.


Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically proven inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) or relapse gastric adenocarcinoma
  • Subjects must be able to take orally
  • Subjects must be confirmed to be PD status by picture diagnosis after first-line chemotherapy using S-1 alone, S-1 + Cisplatinum or S-1 + taxane, except S-1 + CPT-11
  • Within 4 weeks from the diagnosis of PD
  • Total dosage of S-1 at the first-line is over 2,240mg/m2 in S-1 alone treatment, 1,680mg/m2 in the S-1 combination
  • ECOG performance status ≤ 1
  • Follow up Age 20 or over
  • Life expectancy estimated more than 12 weeks
  • Hgb ≥ 8 g/dL, WBC 4,000-12,000/mm3, ANC ≥ 2,000/mm3, platelets ≥ 100,000/mm3
  • Creatinine ≤ upper normal limit (UNL)
  • Total bilirubin ≤ 1.5 X UNL
  • Written informed consent

Exclusion Criteria:

  • S-1 + CPT-11 was employed as a first-line
  • Any other cytotoxic agents therapy, immuno-therapy, radiation-therapy
  • After S-1 adjuvant
  • Suspended cases by adverse events by S-1 or S-1 combination
  • Excessive amounts of ascites require drainage
  • Known brain metastases
  • History of hypersensitivity to fluoropyrimidines and CPT-11
  • Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant
  • Active double cancer
  • Gastrointestinal bleeding
  • Any subject judged by the investigator to be unfit for any reason to participate in the study
  Contacts and Locations
Please refer to this study by its identifier: NCT00639327

  Show 86 Study Locations
Sponsors and Collaborators
Japan Clinical Cancer Research Organization
Taiho Pharmaceutical Co., Ltd.
Principal Investigator: Masashi Fujii, M.D.,PhD Surugadai Nihon University Hospital
  More Information

No publications provided

Responsible Party: Masashi Fujii/Associate Professor, Department of Digestive Surgery, Surugadai Nihon University Hospital Identifier: NCT00639327     History of Changes
Other Study ID Numbers: JACCRO GC-05
Study First Received: March 5, 2008
Last Updated: June 27, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Japan Clinical Cancer Research Organization:
Stomach Neoplasms
Second line chemotherapy
Refractory to S-1
S-1 and Irinotecan Combination
Phase III study

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 14, 2014